Drug compositions

ABSTRACT

Described herein are pharmaceutical compositions including a proton pump inhibitor and an antiparasitic drug. In some embodiments, the compositions can be formulated as a non-solid for oral administration. The compositions can be used to treat gastrointestinal conditions. Methods of treatment using the compositions are also described.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a divisional patent application of U.S. patentapplication Ser. No. 15/675,435, filed Aug. 11, 2017, which claims thebenefit of U.S. provisional patent application No. 62/373,871, filedAug. 11, 2016, the entire disclosure of which is incorporated herein byreference.

FIELD

Described herein are compositions including combination therapy fortreating gastrointestinal conditions.

SUMMARY

Described herein are pharmaceutical compositions useful for treatingand/or preventing gastrointestinal conditions/discomfort in mammals.Mammals can include, but are not limited to humans, horses, camels,dogs, cats, cows, bears, rodents, sheep, goats, pigs and the like. Insome embodiments, the compositions described herein can be consideredveterinary compositions. In some embodiments, the compositions caninclude a synergistic combination of drugs and/or have an additive drugeffect and can be termed combination therapy. In some embodiments, thecombination therapy can include a proton pump inhibitor such as agastric reflux drug/gastric ulcer drug and an antiparasitic drug.

The compositions can include, combined, a proton pump inhibitor and anantiparasitic drug. In one embodiment, the proton pump inhibitor isomeprazole. In another embodiment, the antiparasitic drug isfenbendazole. In some embodiments, the proton pump inhibitor is presentat a concentration of about 22% w/v and/or the antiparasitic drug ispresent at a concentration of about 30% w/v.

Combining omeprazole with fenbendazole can provide a surprisingsynergistic effect that can reduce gastrointestinal recovery time and/orreduce the amount of drugs to achieve a similar or better result whencompared to a single drug.

In some embodiments, the composition is formulated as a non-solid fororal administration. The non-solid can be a liquid or a paste.

The compositions can further include polyethylene glycol, sodiumsulfite, carboxymethyl cellulose, and/or sodium bicarbonate.

Methods of treating a gastrointestinal ulcer are also described. Themethods can comprise administering a composition including the protonpump inhibitor and the antiparasitic drug to a mammal having thegastrointestinal ulcer.

In some embodiments, the administration is performed using an oralsyringe.

In some embodiments, the mammal is a human, a horse, or a camel. In someembodiments, the mammal is an athlete.

Methods of forming a composition including a proton pump inhibitor andan antiparasitic drug are also described. The methods can comprisemixing a combination including the proton pump inhibitor and theantiparasitic drug in a melted base agent to form the composition.

In some embodiments, the melted base agent is polyethylene glycol. Themixed composition can also optionally include a preservative and/or awetting agent.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 illustrates a horse's stomach lining. Dark pitting and roughedges on the horse's stomach lining can be seen. The horse had a Grade 2ulcer and was being treated ineffectively with a commercially availabledrug.

FIG. 2 illustrates another horse's stomach lining. Dark pitting andrough edges on the lining of this horse's stomach can be seen. The horsehad a Grade 2 ulcer and was being treated ineffectively with the samecommercially available drug.

FIG. 3 illustrates the horse's stomach from FIG. 2 17 days afterbeginning treatment with the present compositions. The stomach liningafter 17 days is now smooth and has no more dark pitting.

FIG. 4A is a Grade 4 ESDG in a three year old thoroughbred filly (TBfilly) before treatment and FIG. 4B is a Grade 0 ESDG in the same threeyear old TB filly after treatment.

FIG. 5A is a Grade 4 ESDG in a four year old TB filly before treatmentand FIG. 5B is a Grade 0 ESDG in the same four year old TB filly aftertreatment.

FIGS. 6A and 6B illustrate an ESDG in a horse before treatment and FIGS.6C and 6D illustrate a Grade 0 ESDG in the same horse after treatment.

FIGS. 7A and 7B illustrate an ESDG in a second horse before treatmentand FIGS. 7C and 7D illustrate a Grade 0 ESDG in the same horse aftertreatment.

FIGS. 8A and 8B illustrate an ESDG in a third horse before treatment andFIGS. 8C and 8D illustrate a Grade 0 ESDG in the same horse aftertreatment.

DETAILED DESCRIPTION

Described herein are pharmaceutical compositions useful for treatinggastrointestinal conditions in mammals. Gastrointestinal conditions caninclude ulcers, reflux conditions, and the like. In some embodiments,the herein described pharmaceutical compositions can be used to treatand/or prevent an ulcer.

Mammals can include, but are not limited to, humans, horses, camels,dogs, cats, cows, bears, rodents, oxen, bison, buffalo, caribou, moose,deer, elk, sheep, goats, pigs, rabbits, pouched mammals, primates,carnivores, and the like.

In some embodiments, the mammals can be athletes. Athletes can include,but are not limited to, race horses, race camels, race dogs, racinghumans, jumping horses, jumping camels, jumping dogs, jumping humans,dancing horses, dancing camels, dancing dogs, dancing humans, and thelike. In other embodiments, the mammals can be working mammals. Workingmammals can include, but are not limited to, mammals that exert physicalenergy for a purpose. That purpose can be pulling a load, pushing aload, carrying a load, carrying a human, jumping, dancing, climbing,swimming, and the like.

In some embodiments, the mammal is a thoroughbred horse. Thoroughbredscan include, but are not limited to Arabians, Standardbreds, QuarterHorses, and the like.

Prior to discovery of the present compositions, treatment ofgastrointestinal conditions, such as an ulcer, took at least four weeksto mitigate, reduce, or diminish the condition. In some cases, treatmentcould take as long as a year. In other cases, treatment would be ongoingindefinitely. In some cases, the longer a mammal is subjected totreatment with particular drugs, the more side effects the mammal may besubjected to.

The present combinations can produce synergistic and/or additive effectsin reducing a symptom associated with a gastrointestinal condition.Consequently, a considerably reduced dose of therapeutic compounds canbe given for an equivalent effect for each individual therapeuticcompound or an equivalent amount of each therapeutic compound can begiven to achieve a larger and/or more rapid response. In someembodiments, the compositions can reduce side-effects and drug burden.

As used herein, the term “pharmaceutical composition” refers to atherapeutically effective concentration of the drugs and otheringredients described herein. As used herein, the term “pharmaceuticallyacceptable” refers to compositions that do not produce an adverse,allergic, or other untoward or unwanted reaction when administered to amammal.

The drug combination or combination therapy disclosed herein can beformulated in any appropriate form. An appropriate from can be a formthat is easy to administer, allows the stability of active agent(s),allows the introduction of active agent(s), and the like. Appropriateforms can include powders, semi-solids, liquids, pastes, suspensions,inhalable dry powders, inhalable formulations, solids, granules,combinations thereof, and the like.

The drug combination or combination therapy disclosed herein may be madeinto a semi-solid formulation. Semi-solid formulations can be made forenteral or topical administration. Semi-solid formulations suitable forenteral administration include, without limitation, pastes, and gels.Semi-solid formulations suitable for topical or oral administrationinclude, without limitation, ointments, creams, salves, pastes, andgels. The drug combination or combination therapy disclosed hereinintended for such administration may be prepared according to any methodknown in the art for the manufacture of pharmaceutical compositions.

The drug combination or combination therapy may be made into a liquidformulation. Liquid formulations suitable for enteral or parenteraladministration include, without limitation, solutions, syrups, elixirs,dispersions, emulsions, and suspensions. The drug combination orcombination therapy disclosed herein intended for such administrationmay be prepared according to any method known in the art for themanufacture of pharmaceutical compositions. In such liquid dosage forms,the drug combination disclosed herein may be admixed with (a) suitableaqueous and non-aqueous carriers, (b) diluents, (c) solvents, such as,e.g., water, ethanol, propylene glycol, polyethyleneglycol, glycerol,vegetable oils, such as, e.g., rapeseed oil and olive oil, andinjectable organic esters such as ethyl oleate; and/or fluidity agents,such as, e.g., surfactants or coating agents like lecithin. In the caseof dispersions and suspensions, fluidity can also be controlled bymaintaining a particular particle size.

Liquid and/or semi-solid formulations may be formulated with sweeteningagents, for example glycerol, propylene glycol, sorbitol or sucrose.Such formulations may also contain one or more demulcent, preservative,flavoring agent, and/or coloring agent.

Liquid and/or semi-solid suspensions may be formulated by suspending thedrug combination in an admixture with suitable excipients. Suitableexcipients can be suspending agents, such as sodium carboxymethylcellulose, methylcellulose, hydroxypropylmethylcellulose, sodiumalginate, pectin, polyvinyl pyrrolidone, polyvinyl alcohol, natural gum,agar, gum tragacanth, and/or gum acacia.

Oily suspensions may be formulated by suspending the drug combination inan admixture with (a) vegetable oils including almond oil, arachis oil,avocado oil, canola oil, castor oil, coconut oil, corn oil, cottonseedoil, grape seed oil, hazelnut oil, hemp oil, linseed oil, olive oil,palm oil, peanut oil, rapeseed oil, rice bran oil, safflower oil, sesameoil, soybean oil, soya oil, sunflower oil, walnut oil, wheat germ oil,or a combination thereof, (b) a saturated fatty acid, an unsaturatedfatty acid, or a combination thereof, such as palmitic acid, stearicacid, oleic acid, linoleic acid, linolenic acid, or a combinationthereof, (c) mineral oil such as liquid paraffin, (d) surfactants ordetergents. The oily suspensions may contain a thickening agent such asbeeswax, hard paraffin, or cetyl alcohol.

In some embodiments, oils can be used as a carrier or in the place of acarrier such as polyethylene glycol. The drug combination disclosedherein may be made into an inhaled formulation. Inhaled formulationssuitable for enteral or parenteral administration include, withoutlimitation, aerosols and/or dry powders. The drug combination disclosedherein intended for such administration may be prepared according to anymethod known in the art for the inhalable manufacture of pharmaceuticalcompositions.

The drug combination may be made into a solid formulation. Solidformulations suitable for enteral or parenteral administration include,without limitation, capsules, tablets, pills, troches, lozenges, powdersand granules suitable for inhalation, ingestion, or for reconstitutioninto sterile injectable solutions or dispersions. In other embodiments,the drug combination can be in a semi-solid form such as a paste. Thedrug combination intended for such administration may be preparedaccording to any method known to the art for the manufacture ofpharmaceutical compositions. In such solid dosage forms, the drugcombination may be admixed with (a) at least one inert customaryexcipient (or carrier), such as, e.g., sodium citrate or dicalciumphosphate or (b) fillers or extenders, such as for example, starch,lactose, sucrose, glucose, mannitol, isomalt, and silicic acid, (c)binders, such as, e.g., carboxymethylcellulose, alignates, gelatin,polyvinylpyrrolidone, sucrose and acacia, (d) humectants, such as, e.g.,glycerol, (e) disintegrating agents, such as, e.g., agar-agar, calciumcarbonate, corn starch, potato starch, tapioca starch, alginic acid,certain complex silicates and sodium carbonate, (f) solution retarders,such as, e.g., paraffin, (g) absorption accelerators, such as, e.g.,quaternary ammonium compounds, (h) wetting agents, such as, e.g., cetylalcohol and glycerol monostearate, (i) adsorbents, such as, e.g., kaolinand bentonite, (j) lubricants, such as, e.g., talc, stearic acid,calcium stearate, magnesium stearate, solid polyethylene glycols, sodiumlauryl sulfate or mixtures thereof, and (k) buffering agents. Thetablets may be uncoated or they may be coated by known techniques todelay disintegration and absorption in the gastrointestinal tract andthereby provide a sustained action over a longer period.

In some embodiments, the compositions can include a proton pumpinhibitor such as a gastric reflux drug/gastric ulcer drug incombination with an antiparasitic drug. In some embodiments, theantiparasitic drug can be included in the composition at most about 35%(w/v), at most about 40% (w/v), about 15% (w/v), about 20% (w/v), about25% (w/v), about 30% (w/v), about 35% (w/v), about 40% (w/v), about 45%(w/v), about 50% (w/v), between about 20% and about 40% (w/v), orbetween about 25% and about 35% (w/v). In some embodiments, the gastricreflux drug/gastric ulcer drug can be included in the composition atmost about 30% (w/v), at most about 25% (w/v), about 10% (w/v), about15% (w/v), about 20% (w/v), about 21% (w/v), about 22% (w/v), about 23%(w/v), about 25% (w/v), about 30% (w/v), about 35% (w/v), about 40%(w/v), between about 20% and about 25% (w/v), or between about 15% andabout 30% (w/v).

In one embodiment, the gastric reflux drug/gastric ulcer drug isomeprazole. In one embodiment, the antiparasitic drug is fenbendazole.

Combining omeprazole with fenbendazole can provide a surprisingsynergistic effect that can reduce gastric ulcer recovery time. In otherembodiments, combining omeprazole with fenbendazole can provide asurprising synergistic effect that can reduce recovery time for othergastrointestinal conditions.

A composition disclosed herein may optionally include apharmaceutically-acceptable carrier that facilitates processing of adrug into pharmaceutically-acceptable compositions. Such a carrier canbe mixed with a drug or drugs or permitted to dilute or enclose the drugor drugs and can be a solid, semi-solid, or liquid agent. It isunderstood that the drug or drugs can be soluble or can be delivered asa suspension in the desired carrier or diluent. In some embodiments, thedrugs can be formulated as a paste. Any of a variety of pharmaceuticallyacceptable carriers can be used including, without limitation, aqueousmedia such as, e.g., water, saline, glycine, hyaluronic acid and thelike; solid carriers such as, e.g., polyethylene glycol, polyethyleneoxide, mannitol, lactose, starch, magnesium stearate, sodium saccharin,talcum, cellulose, glucose, sucrose, magnesium carbonate, and the like;solvents; dispersion media; coatings; isotonic and absorption delayingagents; or any other inactive ingredient. Selection of apharmacologically acceptable carrier can depend on the mode ofadministration. In some embodiments, solid carriers can be melted.

In one embodiment, the pharmaceutically-acceptable carrier is a baseagent melted to form a paste. In some embodiments, each base agent canbe included in the composition at most about 10% (w/v), at most about 6%(w/v), about 1% (w/v), about 2% (w/v), about 3% (w/v), about 4% (w/v),about 5% (w/v), about 6% (w/v), about 7% (w/v), about 8% (w/v), about 9%(w/v), about 10% (w/v), between about 1% and about 10% (w/v), or betweenabout 5% and about 7% (w/v).

In one embodiment, the base agent can be a polyethylene glycol.Polyethylene glycol used as a base agent can have a molecular weight ofgreater than about 1,000 g/mol, greater than about 1,200 g/mol, greaterthan about 1,400 g/mol, between about 1,000 g/mol and about 1,600 g/mol,between about 1,300 g/mol and about 1,500 g/mol, or between about 1,400g/mol and about 1,500 g/mol. In one embodiment, the polyethylene glycolhas a molecular weight of about 1,450 g/mol.

A pharmaceutical composition disclosed herein can optionally include,without limitation, other pharmaceutically acceptable components (orpharmaceutical components), including, without limitation, buffers,preservatives, tonicity adjusters, salts, antioxidants, osmolalityadjusting agents, physiological substances, pharmacological substances,bulking agents, emulsifying agents, wetting agents, flavoring agents,coloring agents, suspension agents, and the like.

Various buffers and means for adjusting pH can be used to prepare apharmaceutical composition disclosed herein. Such buffers include,without limitation, acetate buffers, citrate buffers, phosphate buffers,neutral buffered saline, phosphate buffered saline, bicarbonate buffers,and borate buffers. It is understood that acids or bases can be used toadjust the pH of a composition as needed. Bases can include sodiumhydroxide. In one embodiment, sodium bicarbonate is used as a buffer. Inanother embodiment, sodium hydroxide is used to make the compositionmore alkaline. In some embodiments, the alkalinity of the compositioncan be a pH greater than about 7, greater than about 7.5, greater thanabout 8, greater than about 8.5, greater than about 9, greater thanabout 9.5, or greater than about 10

In some embodiments, a buffer(s) can be included in the composition atmost about 10% (w/v), at most about 5% (w/v), about 1% (w/v), about 2%(w/v), about 3% (w/v), about 4% (w/v), about 5% (w/v), about 6% (w/v),about 7% (w/v), about 8% (w/v), about 9% (w/v), about 10% (w/v), betweenabout 1% and about 10% (w/v), or between about 4% and about 6% (w/v).

Pharmaceutically acceptable antioxidants can include, withoutlimitation, sodium metabisulfite, sodium thiosulfate, acetylcysteine,butylated hydroxyanisole and butylated hydroxytoluene.

Flavoring agents can provide a composition that smells good and/ortastes good. Non-human mammals may need encouragement to consume thecompositions described. Thus, flavoring agents may be added thatstimulate appeal to or that naturally attract a particular mammalspecies. Flavoring agents can make orally administrable compositionstaste like apple, orange, lemon, grape, butterscotch, cherry, blueberry,raspberry, strawberry, honey, peppermint, spearmint, cinnamon, peach,watermelon, chocolate, espresso, mango, banana, carrot, cantaloupe,guava, acai, cheese, tomato, caramel, taffy, lime, and the like. Flavorcombinations can also be provided.

Preservatives can include, without limitation, sodium sulfite, sodiumsulfide, benzalkonium chloride, chlorobutanol, thimerosal,phenylmercuric acetate, phenylmercuric nitrate, a stabilized oxy chlorocomposition and chelants, such as, e.g., DTPA(diethylenetriaminepentaacetic acid) or DTPA-bisamide, calcium DTPA, andCaNaDTPA-bisamide. In one embodiment, sodium sulfite is used as apreservative.

In some embodiments, a preservative(s) can be included in thecomposition at most about 0.2% (w/v), at most about 0.5% (w/v), about0.05% (w/v), about 0.06% (w/v), about 0.07% (w/v), about 0.08% (w/v),about 0.09% (w/v), about 0.1% (w/v), about 0.11% (w/v), about 0.12%(w/v), about 0.13% (w/v), about 0.14% (w/v), about 0.15% (w/v), betweenabout 0.05% and about 0.15% (w/v), or between about 0.09% and about0.11% (w/v).

Tonicity adjustors can include, without limitation, salts such as, e.g.,sodium chloride, potassium chloride, mannitol or glycerin and otherpharmaceutically acceptable tonicity adjustors.

Suspension agents can include, without limitation, carboxymethylcellulose. The suspension agent can be used to keep the drug(s)dispersed evenly in the composition.

In some embodiments, the suspension agent(s) can be included in thecomposition at most about 0.2% (w/v), at most about 0.5% (w/v), about0.05% (w/v), about 0.1% (w/v), about 0.2% (w/v), about 0.3% (w/v), about0.4% (w/v), about 0.5% (w/v), about 0.8% (w/v), about 1% (w/v), betweenabout 0.1% and about 0.3% (w/v), or between about 0.1% and about 1%(w/v).

Wetting agents can include, without limitation, polyethylene glycol. Insome embodiments, the polyethylene glycol can be a low molecular weightpolyethylene glycol. The low molecular weight polyethylene glycol canhave a molecular weight of less than about 500 g/mol, less than about300 g/mol, greater than about 100 g/mol, between about 200 g/mol andabout 400 g/mol, between about 100 g/mol and about 500 g/mol, or betweenabout 250 g/mol and about 350 g/mol. In one embodiment, the polyethyleneglycol has a molecular weight of about 300 g/mol.

In some embodiments, the wetting agent can be included in thecomposition at least about 35% (w/v), at least about 60% (w/v), about35% (w/v), about 40% (w/v), about 50% (w/v), about 60% (w/v), about 65%(w/v), about 70% (w/v), between about 35% and about 40% (w/v), orbetween about 60% and about 70% (w/v).

In one embodiment, a composition can include drugs formulated as a pasteincluding carboxymethyl cellulose, sodium sulfite, sodium bicarbonate,and polyethylene glycol. In some embodiments, a composition can includedrugs formulated as a liquid including carboxymethyl cellulose, sodiumsulfite, sodium bicarbonate, and polyethylene glycol. In one embodiment,a composition can include omeprazole, fenbendazole, carboxymethylcellulose, sodium sulfite, sodium bicarbonate, and polyethylene glycolin solution.

In some embodiments, a composition can be provided as granules. In someembodiments, the granules can be provided as a scoop. A scoop can beprovided as a 30 Scoop, a 60 Scoop, or a 100 Scoop size.

In some embodiments, a composition can be provided as a suspension. Asuspension can be provided as a 480 mL aliquot, a 960 mL aliquot, or a3,785 mL aliquot.

In one embodiment, a composition or combination therapy can includeabout 2.2 g omeprazole, about 3 g fenbendazole, about 0.02 gcarboxymethyl cellulose, 0.01 g sodium sulfite, 0.5 mL sodiumbicarbonate, and about 1.2 g polyethylene glycol in 10 mL of solution.In some embodiments, the formulation is maintained at a pH greater than8.

In some embodiments, a composition can be provided as a 10 mL oral pasteincluding 2.2 g of omeprazole and 3 g of fenbendazole. The compositioncan be stored at a temperature between about 20° C. and about 25° C.

In some embodiments, the composition can be provided in a dial-a-doseoral syringe. In one embodiment, the dial-a-dose syringe is a 30 mLsyringe.

In some embodiments, the compositions can include inactive ingredientssuch as, but not limited to, carboxymethylcellulose, sodium bicarbonate,sodium sulfite, polyethyleneglycol, distilled water, and optionallysodium hydroxide. In other embodiments, each 1 mL of composition caninclude inactive ingredients such as, but not limited to, 2 mg ofcarboxymethylcellulose, 3.8 mg of sodium bicarbonate, 1 mg of sodiumsulfite, 60 mg of polyethyleneglycol 1450, 536 mg of polyethyleneglycol3, distilled water, and optionally sodium hydroxide to adjust pH.

The drug combination or combination therapy disclosed herein may beformulated for either local or systemic delivery using topical, enteral,or parenteral routes of administration.

In some embodiments, the compositions described herein are deliveredorally. When delivered orally, the compositions can be administeredusing an oral medication syringe.

The compositions described herein can be administered at amounts ofabout 10 cc, about 15 cc, about 20 cc, about 25 cc, about 30 cc, about35 cc, about 40 cc, about 45 cc, about 50 cc, about 55 cc, about 60 cc,about 65 cc, about 70 cc, about 75 cc, about 80 cc, about 85 cc, about90 cc, about 95 cc, about 100 cc, at least about 10 cc, at least about20 cc, between about 20 cc and about 50 cc, between about 20 cc andabout 30 cc, between about 25 cc and about 35 cc, between about 30 ccand about 35 cc, or between about 25 cc and about 30 cc peradministration.

Administration can be any interval that results in a therapeuticresponse. In some embodiments, administration can be one, two, three,four, five, or more times per day. In other embodiments, administrationcan be every other day, every third day, every fourth day, every fifthday, every sixth day, once per week, twice per month, monthly, and thelike. In one embodiment, administration is once per day. In still otherembodiments, administration can be for the remaining life of the mammal.

In some embodiments, when the animal is an athlete, administration canbe before an athletic event such, as for example, but not limited toevery day, every other day, every third day, every fourth day, everyfifth day, every sixth day, once per week, twice per month, and the likeleading up to the athletic event.

In other embodiments, when the animal is an athlete, administration canbe after an athletic event such as, for example, but not limited toevery day, every other day, every third day, every fourth day, everyfifth day, every sixth day, once per week, twice per month, and the likeafter the athletic event.

In some embodiments, administration can include both before and after anathletic event. In some embodiments, the administration is the samebefore and after an athletic event. In other embodiments, theadministration is different before and after the athletic event.

Methods of forming administrable compositions are also described.Methods can include first weighing the ingredients for the composition.Then, the polyethylene glycol base agent is heated until it melts. Tothe melted base agent, omeprazole, carboxymethyl cellulose, sodiumsulfite, and fenbendazole are added. The contents are then mixed until asmooth paste is achieved. The paste is wetted as necessary with apolyethylene glycol wetting agent. The pH is checked and adjusted asnecessary using sodium hydroxide (e.g., pellets). In some embodiments,the pH is adjusted to an alkaline pH. In some embodiments, the alkalinepH is greater than about 8. The resulting paste is then pulled into asyringe for storage, sterilization, administration, or the like.

Some embodiments provide a kit including an oral syringe pre-filled witha composition described herein and instruction for use in a unifyingcontainer.

Other embodiments provide a kit including a vial or other appropriatecontainer containing a composition described herein and instruction foruse in a unifying container.

Still other embodiments provide a kit including a vial or otherappropriate container containing a composition described herein, asyringe, and instruction for use in a unifying container.

Some embodiments provide a kit including seven oral syringes pre-filledwith a composition described herein and instruction for a week's use ina unifying container.

Other embodiments provide a kit including a vial or other appropriatecontainer containing a composition described herein for seven days ofuse and instruction for use in a unifying container.

Still other embodiments provide a kit including a vial or otherappropriate container containing a composition described herein forseven days of use, seven oral syringes, and instruction for use in aunifying container.

Once housed in a delivery device or included in a kit, thecomposition/delivery devices/kits can be sterilized using conventionalsterilization techniques without substantial degradation to thecomposition. Without substantial degradation to the composition meansthat the composition retains greater than 80%, greater than 90%, greaterthan 95%, or greater than 99% of its activity. In some embodiments, thecompositions remain unaffected by sterilization. Sterilization can be byat least one sterilization technique including, but not limited to,gamma irradiation, pressure sterilization, and/or steam sterilization.

In some embodiments, the compositions described herein can retainsubstantially all potency for at least 14 days. In some embodiments, thecompositions described herein can retain substantially all potency forat least 30 days. In some embodiments, the compositions described hereincan retain substantially all potency for at least 60 days. In someembodiments, the compositions described herein can retain substantiallyall potency for at least 90 days. In some embodiments, the compositionsdescribed herein can retain substantially all potency for at least 180days. In some embodiments, the compositions described herein can retainsubstantially all potency for at least 360 days. In some embodiments,the compositions described herein can retain substantially all potencyfor longer than 360 days.

Substantially all potency means that the compositions retain at leastgreater than 80%, greater than 90%, greater than 95%, or greater than99% of its activity when stored at appropriate conditions. In someembodiments, appropriate conditions can be at room temperature. In someembodiments, appropriate conditions can be without direct light. In someembodiments, appropriate conditions can be under refrigeration orrefrigerated.

The compositions described herein can reduce incidence time of agastrointestinal condition. In one embodiment, the compositionsdescribed herein can reduce the incidence time of a gastric ulcer. Insome embodiments, the compositions can simply treat an ulcer. Treatmentusing omeprazole alone is generally prescribed for once dailyadministration for four weeks. Many times, omeprazole is prescribed foran additional four week period to fully treat a gastrointestinalcondition. In some instances, omeprazole can be administered to somemammals indefinitely to treat ongoing gastrointestinal conditions. Inthese mammals, omeprazole alone may not fully treat the gastrointestinalcondition, even after eight weeks of treatment.

In some embodiments, the herein described compositions can reduce theincidence time of a gastrointestinal condition when compared totreatment with omeprazole alone by at least about 10%, by at least about20%, by at least about 50%, by at least about 75%, by at least about100%, by at least about 150%, by at least about 200%. In someembodiments, treatment time can be reduced by at least 1 week, at least2 weeks, at least 3 weeks, at least 4 weeks, at least 5 weeks, or atleast 6 weeks. In some embodiments, the herein described compositionscan fully treat a gastrointestinal condition thereby not requiringindefinite treatment.

As a result of the reduced incidence time, a composition disclosedherein may reduce an unwanted side effect elicited by administration ofomeprazole and/or fenbendazole. In one embodiment, unwanted side effectsof omeprazole include, without limitation, anorexia, colic, nausea,vomiting, flatulence, diarrhea, hematologic abnormalities, urinary tractinfections, proteinuria, and/or central nervous system disturbances. Inone embodiment, unwanted side effects of fenbendazole include, withoutlimitation, vomiting, drooling, and/or diarrhea.

Further, as a result of the synergistic and/or additive effects of theherein described compositions, a reduced load of drugs may be requiredto achieve similar results to the drugs alone. In some embodiments,treatment using the described compositions may only require about 10%,about 20%, about 30%, about 40%, about 50%, about 60%, about 70%, orabout 80% of a general dose of omeprazole. In other embodiments,treatment using the described compositions may only require about 10%,about 20%, about 30%, about 40%, about 50%, about 60%, about 70%, orabout 80% of a general dose of fenbendazole.

In some embodiments, compositions described herein can be administeredregularly to aid in preventing an ulcer or other gastrointestinal issue.The compositions can be administered daily after treatment of an ulcerto prevent recurrence of the ulcer. In other embodiments, thecompositions can be administered before evidence of an ulcer exists toprevent an ulcer from ever occurring. I some embodiments, the hereindescribed compositions can be administered for an entire lifetime toprevent the occurrence of ulcers.

In some embodiments, horses can be clinically healed within about 30days of treatment. In other embodiments, horses can be clinically healedin less than about 30 days of treatment. In other embodiments, greaterthan about 80% of horses can be clinically healed within about 30 daysof treatment. In other embodiments, greater than about 80% of horses canbe clinically healed in less than about 30 days of treatment. In otherembodiments, about 80% of horses can be clinically healed after 28 daysof treatment. In some embodiments, clinically healed can mean that ahorse has an ulcer score of Grade 0 or Grade 1. In other embodiments,clinically healed can mean that a horse has an ulcer score of Grade 0.

In other embodiments, about 90% of horses can be clinically healed after30 days of treatment. In other embodiments, greater than about 90% ofhorses can be clinically healed within about 30 days of treatment. Inother embodiments, greater than about 90% of horses can be clinicallyhealed in less than about 30 days of treatment. In other embodiments,about 90% of horses can be clinically healed after 30 days of treatment.

In other embodiments, about 95% of horses can be clinically healed after30 days of treatment. In other embodiments, greater than about 95% ofhorses can be clinically healed within about 30 days of treatment. Inother embodiments, greater than about 95% of horses can be clinicallyhealed in less than about 30 days of treatment. In other embodiments,about 95% of horses can be clinically healed after 30 days of treatment.

In some embodiments, horses can be clinically healed within about 15days of treatment. In other embodiments, horses can be clinically healedin less than about 15 days of treatment. In other embodiments, greaterthan about 80% of horses can be clinically healed within about 15 daysof treatment. In other embodiments, greater than about 80% of horses canbe clinically healed in less than about 15 days of treatment. In otherembodiments, about 80% of horses can be clinically healed after 14 daysof treatment.

In some embodiments, horses can be clinically healed within about 14days of treatment. In other embodiments, horses can be clinically healedin less than about 14 days of treatment. In other embodiments, greaterthan about 80% of horses can be clinically healed within about 14 daysof treatment. In other embodiments, greater than about 80% of horses canbe clinically healed in less than about 14 days of treatment.

In other embodiments, about 90% of horses can be clinically healed after14 days of treatment. In other embodiments, greater than about 90% ofhorses can be clinically healed within about 14 days of treatment. Inother embodiments, greater than about 90% of horses can be clinicallyhealed in less than about 14 days of treatment. In other embodiments,about 90% of horses can be clinically healed after 14 days of treatment.

In other embodiments, about 95% of horses can be clinically healed after14 days of treatment. In other embodiments, greater than about 95% ofhorses can be clinically healed within about 14 days of treatment. Inother embodiments, greater than about 95% of horses can be clinicallyhealed in less than about 14 days of treatment. In other embodiments,about 95% of horses can be clinically healed after 14 days of treatment.

In some embodiments, the herein described compositions can beadministered without the need for rest or reduced training. In anembodiment of treatment of a race horse, the compositions can beadministered during training. In some embodiments, the training can beheavy training in preparation for a race.

In other embodiments, treatment with the herein described compositionscan enhance a patient's ability to perform at an optimal level. In someembodiments, prior treatments require a patient to be treated formonths, years, or even a lifetime. Unlike the herein describedcompositions where a patient can train during treatment, priortreatments can prevent training or optimal performance.

In some embodiments, prior treatments require a patient to be treatedfor months, years, or even a lifetime. Unlike the herein describedcompositions where a patient can train during treatment, priortreatments can prevent training or optimal performance.

In some embodiments, when administered to a racing horse or camel,treatment with the herein described compositions can enhance the animalsperformance when compared to being treated using any prior method and/orcomposition. In some embodiments, the herein described compositions canallow a treated horse or camel to perform at an optimal level within theperiods described herein, whereas a horse or camel treated by any priorcomposition or method can only perform at a diminished level and maynever again achieve optimal performance levels. Thus, in someembodiments, the herein described compositions and methods can increasethe running performance of a horse or camel when compared to priortreatment compositions and methods.

In one embodiment, described is a method for increasing a mammal'sathletic performance, the method including treating a horse's ulcerusing a composition as described herein.

In one embodiment, described is a method for increasing a horse'sathletic performance, the method including treating a horse's ulcerusing a composition as described herein.

In one embodiment, described is a method for increasing a camel'sathletic performance, the method including treating a horse's ulcerusing a composition as described herein.

In one embodiment, described is a method for increasing a human'sathletic performance, the method including treating a horse's ulcerusing a composition as described herein.

In some embodiments, treatment using the herein described compositionscan transform an unfit horse into a winning race horse.

Ulcers described herein are graded on a scale of 0 to 4, 4 being mostsevere and 0 being clinically healed. In some embodiments, a grade of 1can also be considered clinically healed. In some embodiments, a scoreof >1 indicates that a horse has an ulcer(s). A score of <1 but >0 mayindicate that a horse has a healing ulcer despite not exhibiting anactive ulcer.

Example 1 Horse Treatment

Two horses were treated with a composition including 22% w/v omeprazoleand 30% w/v fenbendazole. The horses were started on the compositionwhile already taking GASTROGUARD® (37% w/w omeprazole, Bio-Botanica,Inc., New York) at a dose of half a tube per day. A dose of GASTROGUARD®is generally 4 mg/kg of horse weight. GASTROGUARD® is a paste for horsesthat contains 37% w/w omeprazole. Horses were not responding to theGASTROGUARD® treatment. The horses both presented Grade 2 ulcers whichare characterized by the dark pitting and rough edges of the stomachlining illustrated in FIGS. 1-2. The horses had major discomfort.

After just 17 days of treatment using the composition including 22% w/vomeprazole and 30% w/v fenbendazole, each horse was graded normal. Thisnormal grade stomach is illustrated in FIG. 3. FIG. 3 illustrates thatthe stomach lining is now smooth and no dark spots exist.

Example 2 Horse Treatment

Two horses were treated with a composition including 22% w/v omeprazoleand 30% w/v fenbendazole. One horse was a three year old TB Filly thathad a Grade 4 ESDG. FIG. 4A illustrates the severity of the ulcer. After14 days of treatment, the horse presented a Grade 0 ESDG as illustratedin FIG. 4B.

Another horse was a four year old TB Filly that had a Grade 4 ESDG. FIG.5A illustrates the severity of the ulcer. After 28 days of treatment,the horse presented a Grade 0 ESDG as illustrated in FIG. 5B.

Example 3 Camel Treatment

A camel is treated with a composition including omeprazole andfenbendazole. The camel presented a Grade 2 ulcer which is characterizedby the dark pitting and rough edges of the stomach lining. The camel hasmajor discomfort. After just 14 days of treatment using the compositionincluding omeprazole and fenbendazole, the camel presented a stomachthat is graded as normal.

Example 4 Horse Ulcer Prevention

A horse is administered a composition once daily including 22% w/vomeprazole and 30% w/v fenbendazole. The horse presents no signs of anulcer. The horse never develops an ulcer.

Example 5 Horse Ulcer Prevention

A horse is administered a composition twice daily including 22% w/vomeprazole and 30% w/v fenbendazole. The horse presents no signs of anulcer. The horse never develops an ulcer.

Example 6 Horse Ulcer Reoccurrence Prevention

A horse is administered daily a composition including 22% w/v omeprazoleand 30% w/v fenbendazole after being treated for an ulcer. At theinitiation of treatment, the horse presents no signs of an ulcer. Thehorse does not develop a reoccurrence of the ulcer during the year oftreatment.

Example 7 Scoop Preparation

A scoop is prepared that includes 2.2 g of omeprazole USP powder 99.47,3 g of fenbendazole EP powder 100.5, 0.852 g green apple flavor #6005(sugar free), and 16.52 g of dextrose USP anhydrous powder. The contentsare weighed and mixed together one at a time: omeprazole, fenbendazole,apple flavor, and dextrose. The powders are blended until an even colorand smooth mixture (free of clumps) is obtained throughout the mixture.Then 677.16 g of the mixture is dispensed into 32 oz jars with a 30 ccscoop.

Example 8 Suspension Preparation

A suspension is prepared that includes 140.8 g of omeprazole USP powder99.47, 28.8 mL aqueous green apple flavor (sugar free), 0.96 g of sodiumsulfite FCC powder 99.14, 96 mL of sodium bicarbonate, 3.36 g ofcarboxymethylcellulose NA (medium), 192 g of fenbendazole EP powder100.5, and 960 mL of polyethylene glycol 300 NF liquid. The contents areweighed and mixed together one at a time: omeprazole, sodium sulfite,carboxymethylcellulose, apple flavor, and ranitidine. To an appropriatesized beaker is added 50% total volume of the polyethylene glycol. Then,omeprazole, sodium sulfite, apple flavor, and ranitidine are added andthen blended. Sodium bicarbonate is added to the mixture andmixed/blended until uniform. Carboxymethylcellulose is added to themixture and mixed/blended until uniform. The pH is checked and adjustedto pH level 9-10.5 using NaOH or HCl.

Example 9 Horse Treatment

A 4 year old Thoroughbred Gelding was treated at a barn on the backsideof Churchill Downs racetrack in Louisville, Ky. The horse was currentlyin training. The horse was treated with a composition including 2.2 gm/3gm/10 mL of Omeprazole/fenbendazole each day during the treatmentperiod. FIGS. 6A and 6B illustrate scopes of the horse's ulcer atinitiation of treatment. FIGS. 6C and 6D illustrate re-scopes of theulcerated area 14 days after initiation of treatment wherein the horsewas clinically healed and its ulcer graded at zero.

Example 10 Horse Treatment

A 4 year old Thoroughbred Colt was treated at a barn on the backside ofChurchill Downs racetrack in Louisville, Ky. This second horse wascurrently in training. The horse was treated with a compositionincluding 2.2 gm/3 gm/10 mL of Omeprazole/fenbendazole each day duringthe treatment period. FIGS. 7A and 7B illustrate scopes of the horse'sulcer at initiation of treatment. This second horse ran (raced) duringtreatment without adverse effects. FIGS. 7C and 7D illustrate re-scopesof the ulcerated area 14 days after initiation of treatment wherein thehorse was clinically healed and its ulcer graded at zero.

Example 11 Horse Treatment

A 3 year old Thoroughbred Colt was treated at a barn on the backside ofChurchill Downs racetrack in Louisville, Ky. The horse was currently intraining. The horse was treated with a composition including 2.2 gm/3gm/10 mL of Omeprazole/fenbendazole each day during the treatmentperiod. FIGS. 8A and 8B illustrate scopes of the horse's ulcer atinitiation of treatment. FIGS. 8C and 8D illustrate re-scopes of theulcerated area 14 days after initiation of treatment wherein the horsewas clinically healed and its ulcer graded at zero.

Example 12 Horse Treatment

A 3 year old, California bred Chestnut Filly is treated at a barn in DelMar, Calif. The horse currently trains and exhibits a Grade 3 ulcer. Thehorse is treated with a paste composition including 2.2 gm/3 gm/10 mL ofOmeprazole/fenbendazole each day during the treatment period. Afterinitiation of treatment, this horse wins a race at Del Mar, despite notbeing able to win prior to treatment.

Unless otherwise indicated, all numbers expressing quantities ofingredients, properties such as molecular weight, reaction conditions,and so forth used in the specification and claims are to be understoodas being modified in all instances by the term “about.” Accordingly,unless indicated to the contrary, the numerical parameters set forth inthe specification and attached claims are approximations that may varydepending upon the desired properties sought to be obtained by thepresent invention. At the very least, and not as an attempt to limit theapplication of the doctrine of equivalents to the scope of the claims,each numerical parameter should at least be construed in light of thenumber of reported significant digits and by applying ordinary roundingtechniques. Notwithstanding that the numerical ranges and parameterssetting forth the broad scope of the invention are approximations, thenumerical values set forth in the specific examples are reported asprecisely as possible. Any numerical value, however, inherently containscertain errors necessarily resulting from the standard deviation foundin their respective testing measurements.

The terms “a,” “an,” “the” and similar referents used in the context ofdescribing the invention (especially in the context of the followingclaims) are to be construed to cover both the singular and the plural,unless otherwise indicated herein or clearly contradicted by context.Recitation of ranges of values herein is merely intended to serve as ashorthand method of referring individually to each separate valuefalling within the range. Unless otherwise indicated herein, eachindividual value is incorporated into the specification as if it wereindividually recited herein. All methods described herein can beperformed in any suitable order unless otherwise indicated herein orotherwise clearly contradicted by context. The use of any and allexamples, or exemplary language (e.g., “such as”) provided herein isintended merely to better illuminate the invention and does not pose alimitation on the scope of the invention otherwise claimed. No languagein the specification should be construed as indicating any non-claimedelement essential to the practice of the invention.

Groupings of alternative elements or embodiments of the inventiondisclosed herein are not to be construed as limitations. Each groupmember may be referred to and claimed individually or in any combinationwith other members of the group or other elements found herein. It isanticipated that one or more members of a group may be included in, ordeleted from, a group for reasons of convenience and/or patentability.When any such inclusion or deletion occurs, the specification is deemedto contain the group as modified thus fulfilling the written descriptionof all Markush groups used in the appended claims.

Certain embodiments of this invention are described herein, includingthe best mode known to the inventors for carrying out the invention. Ofcourse, variations on these described embodiments will become apparentto those of ordinary skill in the art upon reading the foregoingdescription. The inventor expects skilled artisans to employ suchvariations as appropriate, and the inventors intend for the invention tobe practiced otherwise than specifically described herein. Accordingly,this invention includes all modifications and equivalents of the subjectmatter recited in the claims appended hereto as permitted by applicablelaw. Moreover, any combination of the above-described elements in allpossible variations thereof is encompassed by the invention unlessotherwise indicated herein or otherwise clearly contradicted by context.

Furthermore, numerous references have been made to patents and printedpublications throughout this specification. Each of the above-citedreferences and printed publications are individually incorporated hereinby reference in their entirety.

In closing, it is to be understood that the embodiments of the inventiondisclosed herein are illustrative of the principles of the presentinvention. Other modifications that may be employed are within the scopeof the invention. Thus, by way of example, but not of limitation,alternative configurations of the present invention may be utilized inaccordance with the teachings herein. Accordingly, the present inventionis not limited to that precisely as shown and described.

We claim:
 1. A method of treating a gastrointestinal ulcer, the methodcomprising: administering a composition including a proton pumpinhibitor and an antiparasitic drug to a mammal having thegastrointestinal ulcer, and treating the gastrointestinal ulcer.
 2. Themethod of claim 1, wherein the proton pump inhibitor is omeprazole. 3.The method of claim 1, wherein the proton pump inhibitor is present at aconcentration of about 22% w/v.
 4. The method of claim 1, wherein theantiparasitic drug is fenbendazole.
 5. The method of claim 1, whereinthe antiparasitic drug is present at a concentration of about 30% w/v.6. The method of claim 1, wherein the administration is performed usingan oral syringe.
 7. The method of claim 1, wherein the mammal is ahuman, a horse, or a camel.
 8. A method of forming a composition, themethod comprising: mixing a combination including a proton pumpinhibitor and an antiparasitic drug in a melted base agent to form thecomposition.
 9. The method of claim 18, wherein the melted base agent ispolyethylene glycol.
 10. The method of claim 18, further includingmixing a preservative, wetting agent, or a preservative and a wettingagent.